tbuckley/cabot-search huggingface dataset:
The patient's needs before and six months after the initiation of breast cancer treatment: A prospective study in 600 breast cancer patients.
Authors: Mateja Kurir Borovcic, Zlatka Mavric, Tina Zagar, Vesna Homar, Nena Kopcavar Gucek, Andreja Cirila Skufca Smrdel, Jana Knific, Simona Borstnar, Tanja Marinko, Lorna Zadravec Zaletel, Natasa Kos, Branka Strazisar, Tatjana Slapar, Denis Mastnak Mlakar, Nina Kovacevic, Vedran Hadzic, Bojan Pelhan, Marko Sremec, Tina Rozman, Nikola Besic
Journal: Journal of Clinical Oncology (2022)

e24062 Background: Our aim was to determine the frequency of health-related problems faced by breast cancer patients before and six months after the initiation of breast cancer treatment. Methods: This prospective study involved 600 female breast cancer patients (26-65 years, mean 52), who participated in the pilot study in the novel individualized integrated rehabilitation programme in 2019-2022 and were followed for at least six months. The patients completed three questionnaires (EORTC QLQ - C30, B23 and NCCN) before the initiation of cancer treatment and six months after. The patients received neoadjuvant chemotherapy in 22% of the cases, tumorectomy in 53%, mastectomy in 39%, breast reconstruction in 27%, sentinel node biopsy in 67%, lymphadenectomy in 23%, external beam radiotherapy in 73%, chemotherapy in 45%, anti-HER-2 therapy in 11% and hormonal therapy in 74% of the cases. Data on the patients’ demographics, disease extent, cancer treatment and problems reported in the questionnaires were collected and analysed using descriptive analysis. Results: The problems reported by patients before the initiation of cancer treatment and after six months are presented in Table. In 14 out of 22 parameters, the frequency of problems increased in the six months after the initiation of treatment: fatigue, insomnia, lymphedema, shoulder movement impairment, disturbing scars, heart problems, hot flashes/sweating, gynaecological problems, sexual problems, body image worries, inappropriate nutrition, pain in the shoulder or arm, alopecia and concerns about returning to work. On the other hand, the frequency of problems decreased six months after the initiation of cancer treatment in 6 out of 22 parameters. Our patients less often had depression or anxiety, were too little physically active, smoked, consumed alcohol or used food supplements than before. Conclusions: Six months after the initiation of breast cancer treatment patients have more problems than at the time before treatment.[Table: see text]
A binational cancer registry analysis of Hispanic patients in Mexico and the United States.
Authors: Arturo Lopez Pineda, Josue Abinadi Garrido-Sanchez, Gilberto Gonzalez-Arroyo, Cleto Alvarez-Aguilar
Journal: Journal of Clinical Oncology (2022)

e22513 Background: A marked disparity in cancer burden exists between regions of the world. This global picture can only be obtained because of data obtained from population-based cancer registries, which allow estimates for different geographic areas. We investigate the data differences, clinical characteristics, tumor information, and patient outcomes of Hispanic patients in North America. Methods: We used data from Mexico’s National Cancer Registry and the United States Surveillance, Epidemiology, and End Results Program (SEER) program with four years of follow-up on each registry. of Mexican registry, we excluded outliers and records with more than 80% missing variable; of the United States registry, only patients identified as hispanic or latino were included. On the Mexican registry we re-coded all variables and the United States registry data on secondary neoplasm was excluded to match boths registry. Baseline characteristics and a geographical information system was constructed to map cancer registries and their relative frequencies. A survival analysis was done to understand the correlation between covariates. Lastly, we build machine learning models to predict 3-year overall survival. Results: The Hispanic cancer database (HCB) consists of 291,178 patients (19,904 from Mexico, and 271,274 from the United States). The top three most frequent cancer types were breast, prostate and hematological. The age of diagnosis was 55±17 years. Mexico has a slight skewness towards the earlier age of diagnosis of females. The registries with the highest burden of cancer were New Mexico (USA) and Baja California Sur (Mexico). Average survival months seem very stable across registries in the United States, but not in Mexico. Our linear regression model achieved a coefficient of determination (R-squared) of 0.49, while the logistic regression achieved an AUC of 0.82, with an F1-score of 0.88. Conclusions: Cancer registries are important tools for prevention and development of control programs. Hispanics are a traditionally neglected population in oncological clinical trials, with low enrollment of patients outside of the United States. Mexico enacted its National Cancer Registry Law in 2017, which alongside the Hispanic data on the SEER program in the United States offers enormous opportunities for continued collaboration and understanding of cancer. Both Mexico and the United States can strengthen their cancer prevention strategies and generate trans-border collaboration, research, and patient-support networks.
WheatCENet: A Database for Comparative Co-Expression Networks Analysis of Allohexaploid Wheat and Its Progenitors
Authors: Zhongqiu Li, Yiheng Hu, Xuelian Ma, Lingling Da, Jiajie She, Yue Liu, Xin Yi, Yaxin Cao, Wenying Xu, Yuannian Jiao, Zhen Su
Journal: Genomics Proteomics & Bioinformatics (2022)

Genetic and epigenetic changes after polyploidization events could result in variable gene expression and modified regulatory networks. Here, using large-scale transcriptome data, we constructed co-expression networks for diploid, tetraploid, and hexaploid wheat species, and built a platform for comparing co-expression networks of allohexaploid wheat and its progenitors, named WheatCENet. WheatCENet is a platform for searching and comparing specific functional co-expression networks, as well as identifying the related functions of the genes clustered therein. Functional annotations like pathways, gene families, protein-protein interactions, microRNAs (miRNAs), and several lines of epigenome data are integrated into this platform, and Gene Ontology (GO) annotation, gene set enrichment analysis (GSEA), motif identification, and other useful tools are also included. Using WheatCENet, we found that the network of WHEAT ABERRANT PANICLE ORGANIZATION 1 (WAPO1) has more co-expressed genes related to spike development in hexaploid wheat than its progenitors. We also found a novel motif of CCWWWWWWGG (CArG) specifically in the promoter region of WAPO-A1, suggesting that neofunctionalization of the WAPO-A1 gene affects spikelet development in hexaploid wheat. WheatCENet is useful for investigating co-expression networks and conducting other analyses, and thus facilitates comparative and functional genomic studies in wheat. WheatCENet is freely available at http://bioinformatics.cpolar.cn/WheatCENet and http://bioinformatics.cau.edu.cn/WheatCENet.
Long term evaluation of the Argus-T® adjustable male sling: A prospective study
Authors: R. Zanotti, A.C.M. Costa Matos, F.P. Pinho, C.H.T. Hideki Toi, S.P. Paolillo, G.D. Demartino, M.T. Takada, B.H. Hirata, L.G.M.T. Morato De Toledo
Journal: European Urology (2022)
LGG-24. Neurocognitive impairment and functional independence in adult survivors of childhood glioma: A report from the Childhood Cancer Survivor Study (CCSS)
Authors: Chiara Papini, Mengqi Xing, Sedigheh Mirzaei Salehabadi, Ingrid Tonning Olsson, Katharine Lange, Peter de Blank, Ralph Salloum, Deo Kumar Srivastava, Wendy M Leisenring, Rebecca M Howell, Kevin Oeffinger, Leslie L Robison, Gregory T Armstrong, Kevin R Krull, Tara M Brinkman
Journal: Neuro-Oncology (2022)

Abstract PURPOSE: Survivors of pediatric glioma are at risk of developing physical and neurocognitive sequelae secondary to their tumor and its treatment. The contribution of these conditions to attainment of functional independence has not previously been examined. METHODS: 1,284 adult survivors of pediatric glioma (48% male, median [range] 30 [18-51] years at assessment, 22 [15-34] years since diagnosis) completed the CCSS Neurocognitive Questionnaire with impairment defined as scores &amp;gt; 90th %ile of sibling norms. Treatment exposures were categorized as surgery only, chemotherapy (± surgery), or cranial radiation (± chemotherapy/surgery). Self-reported chronic health conditions (CHCs) were graded by organ system using NCI’s CTCAE v4.3. Latent class analysis utilized six factors (employment, marital status, independent living, driver’s license, assistance with routine needs, assistance with personal care needs) to identify classes of functional independence. Multivariable modified Poisson regression evaluated relative risk (RR) of neurocognitive impairment between the classes, adjusting for sex, race, age at assessment, and age at diagnosis. Path analysis explored the impact of treatment exposures on functional independence, mediated by Grade 2-4 CHCs and neurocognitive impairment. RESULTS: Three latent classes of functional independence were identified: independent (58%), moderately independent (20%), and non-independent (22%). Compared to the independent class, non-independent survivors were at elevated risk for impaired task efficiency (RR=3.86, 95% CI, 2.97-5.01), memory (RR=2.39, 95% CI, 1.91-2.98), organization (RR=2.04, 95% CI, 1.64-2.54), and emotional regulation (RR=1.67, 95% CI, 1.30-2.15). Path analysis revealed significant direct paths from cranial radiation (β=0.14), impaired task efficiency (β=0.42), and sensorimotor (β=0.22) and endocrine conditions (β=0.24) to non-independence. Cranial radiation also was indirectly associated with non-independence through impaired task efficiency (β=0.06), and sensorimotor (β=0.06) and endocrine conditions (β=0.10). CONCLUSIONS: Neurocognitive impairment and chronic health conditions partially mediate the association between treatment exposures and attainment of independence in adulthood, identifying potential intervention targets to promote independence in long-term survivors.
Adding ovarian function suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or resume menstruation after chemotherapy: 8-year follow-up of the randomized ASTRRA trial.
Authors: Soo Yeon Baek, Woo Chul Noh, Sei-Hyun Ahn, Hyun-Ah Kim, Jai Min Ryu, Seung Il Kim, Eun-Gyeong Lee, Seock-Ah Im, Yongsik Jung, Min Ho Park, Kyong Hwa Park, Su Hwan Kang, Joon Jeong, Eunhwa Park, Sung Yong Kim, Min Hyuk Lee, Lee Su Kim, Woosung Lim, Seonok Kim, Hee Jeong Kim
Journal: Journal of Clinical Oncology (2022)

506 Background: Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy (ASTRRA) trial, at 63 months median follow-up, showed that the addition of 2 years of ovarian function suppression (OFS) to Tamoxifen (TAM) significantly improved disease-free survival (DFS) compared with TAM alone in patients with hormone receptor–positive breast cancer who remain in a premenopausal state or resume ovarian function after chemotherapy. We report updated long-term outcomes from ASTRRA trial with 106.4 months median follow-up. Methods: This study is a post-trial follow-up of the ASTRRA trial, which randomly assigned 1,298 patients with breast cancer in a 1:1 ratio to receive TAM only (n = 647) or TAM + OFS (n = 635). The primary endpoint was DFS and secondary endpoint was overall survival (OS). We used Kaplan-Meier estimates for time to event endpoints and hazard ratios (HR) with 95% confidence interval (CI) from Cox-regression model. Results: At 106.4 months of median follow-up, there continues to be a statistically significant reduction in DFS event rate in favor of the TAM+OFS group. The estimated 8-year DFS rate was 85.4% in the TAM + OFS group and 80.2% in the TAM-only group (HR 0.67; 95% CI, 0.51 to 0.87). There were no significant differences in OS between two groups. The estimated 8-year OS rate was 96.5% in the TAM + OFS group and 95.3% in the TAM-only group (HR, 0.78; 95% CI, 0.49 to 1.25). The results of DFS and OS between the two groups defined from the time of random assignment to the time of events were also similar. Conclusions: These data demonstrate consistent survival advantages of adding OFS 2 years to TAM treatment over time, with the long-term follow-up reported to date. This study finding suggest that adding OFS to TAM should be considered for those who remain in a premenopausal state or resume ovarian function after chemotherapy. Longer follow-up is needed to fully evaluate the OS benefit.
MEDB-25. Do extracellular vesicles transfer a multidrug resistant phenotype via ABC transporters in medulloblastoma?
Authors: Philippa Wade, Hannah Jackson, Louisa Taylor, Alistair Hume, Ian Kerr, Beth Coyle
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Medulloblastoma is the most common malignant paediatric brain tumour accounting for 20% of all childhood tumours; approximately one-third of patients present with metastatic disease at diagnosis and the outcome for these patients remains very poor. The high frequency of recurrence and metastatic relapse in medulloblastoma supports the idea of intrinsic drug resistance within cells. This work looks at the ATP-binding cassette (ABC) transporters, known to be upregulated in several cancers, and we hypothesise that extracellular vesicles may transfer ABC transporters to surrounding cells, promoting multidrug resistance within tumours. METHODS: The Cavalli dataset, made up of 763 patient samples, was used to assess the gene expression of a number of ABC transporters across medulloblastoma subgroups. ABC transporter gene and protein expression was then further assessed in medulloblastoma cell lines, including drug-tolerant lines, using qPCR and western blot. Cell viability analysis was used to assess changes in drug response. Matched cell and EV protein samples were used for proteomic analysis. RESULTS: Patient gene expression data showed that high expression of two ABC transporters correlated with reduced patient survival in high-risk subgroups. qPCR analysis of medulloblastoma cell lines showed differential subgroup expression patterns. Additionally, qPCR analysis of drug-tolerant cell lines showed significant increases in the expression of specific drug transporters across the subgroups. RNA-seq confirmed the presence of ABC transporter mRNA in exosomes isolated from high-risk medulloblastoma cell lines. Functional studies of EV transference of ABC transporters are ongoing. CONCLUSIONS: Data to date supports the hypothesis that multidrug transporter carrying extracellular vesicles may transfer their multidrug resistant phenotype to surrounding cells in medulloblastoma, promoting drug resistance. Future work will test this hypothesis by knocking down candidate ABC transporters and assessing the effect on transference of drug resistance by extracellular vesicles.
Alofanib in subsequent therapy for advanced gastric cancer: Final results from the phase Ib clinical trial.
Authors: Ilya Tsimafeyeu, Liubov Yu Vladimirova, Anastasia Mochalova, Natalia Besova, Galina Statsenko, Ivan Rykov, Igor A. Utyashev, Grigory Raskin, Vasily Kazey, Elena Artamonova, Vladimir Moiseyenko, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2022)

e16077 Background: Alofanib (RPT835) is a first-in-class allosteric inhibitor that induces conformational changes in the extracellular domain of FGFR2. Here, we present the final results of the phase Ib clinical study (RPT835GC1B) of alofanib. Methods: Patients with metastatic gastric adenocarcinoma resistant to standard therapy with measurable disease were eligible. The dose finding part used a 3+3 design, starting with a dose level of 50 mg/m2, intravenously, 5 days on, 2 days off. Five dose levels were foreseen. Primary endpoint was maximum tolerated dose (MTD). Secondary endpoints included toxicity, PK, objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). Results: 21 patients were enrolled. 4 (19.1%), 14 (66.7%), 9 (43%), 3 (14.3%), and 12 (57%) patients had ECOG PS 2, ≥2 metastatic sites, liver metastases, bone metastases, and 3-6 lines previous therapy, respectively. The MTD has not been reached and dose of 350 mg/m2 has been declared as recommended phase II dose. With median follow-up of 13.0 months 15 (71.4%) patients had any grade treatment related adverse events (TRAE). Grade 3-4 TRAE occurred in 6 (28.6%) patients. Two (9.5%) patients discontinued treatment due to grade 3 diarrhea and grade 4 reactions immediately after injections. There were no treatment-related deaths in the study. One partial response (5.26%) with a duration of 18.53 months was identified. Disease control rate (DCR) was 68.4% and median duration of stable disease was 4.91 months. Median PFS was 3.63 (95% CI 1.58–5.68) months. Median OS was 7.0 (3.82–10.18) months. 6-month OS rate was 57.1%. OS was almost 2 times better in patients with DCR (median 10.05 vs. 5.9 months) and without bone metastases (8.6 vs. 3.1). Only one patient (4.8%) had FGFR2 amplification (time to death was 7 months). PK parameters linearly changed depending on the dose level, but no correlation with efficacy was found. Table summarizes rate of TRAE and DCR in dose cohorts. Conclusions: Alofanib was feasible and showed early signals of efficacy in heavily-pretreated patients with metastatic gastric cancer. A phase 2 randomized trial is planned. Clinical trial information: NCT04071184. [Table: see text]
SURG-14. Value of the Classification of Intraoperative Adverse Events (ClassIntra) for Resection of CNS Neoplasms in Pediatric and Adolescent Patients
Authors: Richard Drexler, Friederike Fritzsche, Franz Ricklefs, Gertrud Kammler, Thorsten Dohrmann, Rainer Nitzschke, Manfred Westphal, Lasse Dührsen
Journal: Neuro-Oncology (2022)

Abstract OBJECTIVE: Outcome measuring is increasingly important in neurosurgery. Recently, a classification for assessing Intraoperative adverse events (iAE) was introduced (ClassIntra). We aimed to analyze the reliability of the ClassIntra to reflect Intraoperative complications and the potential to predict the outcome of pediatric and adolescent patients who underwent resection of CNS neoplasms. METHODS: A prospective study between 01 July and 31 December 2021 was conducted. The ClassIntra grade for each tumor resection was evaluated at sign-out (Grade 0 to V). Postoperative complications were graded after Clavien-Dindo and Comprehensive Complication Index (CCI). Neurological status was assessed prior surgery and at discharge using Lansky Index, NIHSS, NANO, GCS, and mRS. RESULTS: 21 pediatric and adolescent patients who underwent resection of CNS neoplasms were included. Of these, 8 (38.1%) were female with a mean (SD) age of 9.9 (5.2) years. During 13 (61.9%) resection an iAE was noted, of which 11 (52.4%) were classified as ClassIntra I and 2 (9.5%) as ClassIntra II. The majority (66.7%) underwent surgery for infratentorial pathology, whereas 4 (19.0%) had a supratentorial and 3 (14.3%) a spinal pathology. Preoperative characteristics did not correlate with the severity of ClassIntra. In patients without an iAE, a gross total resection was achieved more frequently (p=0.048). Focusing on postoperative outcome revealed a higher severity of cumulative complications as presented by the CCI (10.4 versus 40.5), longer hospital stay (p=0.04), and higher 30-day readmission rate (p&amp;lt;0.01) in patients with an iAE. However, the neurological outcome and time to begin of adjuvant treatment did not correlate with the ClassIntra. CONCLUSION: Findings of this study suggest that the ClassIntra is sensitive for assessing iAEs and sufficient to identify cases with a higher risk for developing postoperative complications after resection of CNS neoplasms in pediatric and adolescent patients, but cannot predict a possible neurological deterioration.
Use of Menthol Cigarettes, Smoking Frequency, and Nicotine Dependence Among US Youth
Authors: Eric C. Leas, Tarik Benmarhnia, David R. Strong, John P. Pierce
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Menthol may make cigarette smoke less aversive and could lead youth to smoke more frequently and become more dependent on nicotine. <h3>Objective</h3> To assess the association of menthol use with cigarette smoking frequency and nicotine dependence (ND) among youth cigarettes users. <h3>Design, Setting, and Participants</h3> This cohort study used a pooled sample of cohorts of US youth (aged 12-17 years at their baseline and follow-up interviews) in the Population Assessment of Tobacco and Health Study (September 2013 to November 2019). Household interviews were conducted using audio computer-assisted self-interviews. US youth who were past-30-day cigarette smokers at any of wave 2 through wave 5, completed the preceding survey (eg, wave 2 past-30-day cigarette smokers completed wave 1), and indicated whether they used menthol cigarettes were eligible. The association of menthol use with smoking frequency and ND was estimated using inverse probability of treatment weighting adjusted mean differences (aMDs), adjusted risk ratios (aRRs), and corresponding 95% CIs. Data were analyzed from December 2021 to March 2022. <h3>Exposures</h3> Menthol use and transitions in use (switching to or from menthol cigarettes). <h3>Main Outcomes and Measures</h3> Main outcomes were the number of days smoked in the past 30 days, the risk of frequent smoking (smoking ≥20 days in the past 30 days), and symptoms of ND. <h3>Results</h3> There were a total of 1492 observations among 1096 US youth cigarette smokers, of whom 49.4% were female, 67.2% were non-Hispanic White, and 28.7% were aged 12 to 14 years at their baseline survey (all percentages are weighted). Among those who switched from not smoking to smoking (61% of the sample), menthol use was associated with smoking on 3.1 additional days (aMD; 95% CI, 1.9 to 4.2 days), 59% higher risk of being a frequent smoker (aRR, 1.59; 95% CI, 1.23 to 2.06), and 10% higher ND scores (aMD, 1.09; 95% CI, 1.02 to 1.17). Switching from smoking menthol to smoking nonmenthol (vs maintaining menthol use) was associated with smoking on 3.6 fewer days (aMD; 95% CI, −6.3 to −0.9 days) and 47% lower risk of being a frequent smoker (aRR, 0.68; 95% CI, 0.50 to 0.92). <h3>Conclusions and Relevance</h3> These findings suggest that the addition of menthol to cigarettes is associated with increased smoking frequency and ND among US youth.